This research plan deals with a novel aspect of the mechanism of action of carcinogenic nitrosamines and nitrosamides. Most research programs concerned with the metabolism and mode of action have emphasized biochemical activation reactions to yield reactive electrophiles. In order to account for genetically-linked differences in sensitivity to the carcinogen N-methly-N'-nitrosoguanidine in yielding gastric cancer, this research deals with the biochemical denitrosation of MNNG to yield the corresponding methylnitrosoguanidine, a detoxified, inactive metabolite. A resistant species or strain would have higher levels of denitrosation enzyme than a more sensitive strain or species. In addition, differences in sensitivity may be due to capability to repair alkylated DNA and specifically methylated guanidine at the 06 position. This program involves a determination whether this repair process is also related to genetically-linked sensitivity with this compound. Furthermore, the denitrosation of N-nitrosamines, specifically nitrosomorpholine, will be studied as an extension to this class of carcinogens requiring metabolism. Eventually it is planned to extend the studies with animal tissues to tissues obtained from human surgical specimens. Overall this research plan will contribute basic knowledge essential to extrapolate data obtained in animal models to man.